Premature senescence, also known as stress-induced premature senescence, in tumor cells means senescence caused in tumor cells by various stimuli. In contrast to normal cells that undergo senescence after a particular number of cell doublings, cells under tumorigenesis divide uncontrollably without replicative senescence. It has long been known that tumor cells may not undergo cellular senescence. In recent years, however, various stimuli have been known to rapidly induce senescence in tumor cells, which is called stress-induced premature senescence (Sugrue et al., Proc. Natl. Acad. Sci. USA, 94:9648-9653, 1997; Mason et al., Oncogene, 23; 9238-9246, 2004). Representatives among the stress sources capable of inducing senescence in tumor cells are genotoxic chemicals (e.g., etoposide, cyclophophamide, etc.), radiation, and UV light (Hemann and Narita, Genes & Dev., 21:1-5, 2007; Chang et al., Proc. Natl. Acad. Sci. USA, 99: 389-394, 2002).
Suppression of tumor cell growth (proliferation) by inducing senescence in tumor cells through stress-induced premature senescence was suggested as a mechanism for cancer therapy (Roninson et al., Drug Resist Updates, 4:303-313, 2001; Campisi, Science, 309:886-887, 2005), and studies on the mechanism of cellular senescence contributed to an improvement in the efficiency of cancer therapy (Narita and Lowe, Nature Medicine, 11:920-922, 2005). Also, a histological analysis of cancer patients who had the cease of the malignant progression of tumor reported that senescence was effectively induced in tumor cells (Collado et al., Nature, 436:642, 2005). In addition, the tumor suppressor p53 was reported to be implicated in the removal of tumor tissues through cellular senescence, as proven in an animal test (Xue et al., Nature, 445:656-660, 2007). This indicates that cellular senescence can be effectively applied to cancer therapy. In practice, the activation of the senescence mechanism in tumor cells makes it possible to treat cancer with lower doses of anticancer agents or radiation than does the activation of cell death mechanisms, thus improving the side effects associated with conventional cancer therapy and overcoming the resistance of cancer cells to cancer therapy which acquire the resistance to the cell death (Rebbaa, Cancer Lett, 219:1-13, 2005).
There is therefore a need for an anticancer agent based on premature senescence and a method for screening the anticancer agent.
Nowhere have WIG1 (wild-type p53 induced gene-1; ZMAT3, zinc finger matrin type 3), a gene with NCBI Access No. NM—152240 or NM—022470, and YPEL5 [yippee-like 5 (Drosophila)], a gene with NCBI Access No. NM—016061, NM—001127401, NM—001127400, or NM—001127399, been known to be associated with premature senescence in tumor cells in the prior art.